Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABA(A) and GABA(B) Receptors

0531146 - FGÚ 2021 RIV CH eng J - Článek v odborném periodiku
Kubová, Hana - Bendová, Z. - Moravcová, S. - Pačesová, D. - Rocha, L. - Mareš, Pavel
Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABA(A) and GABA(B) Receptors.
International Journal of Molecular Sciences. Roč. 21, č. 9 (2020), č. článku 3184. E-ISSN 1422-0067
Grant CEP: GA ČR(CZ) GA19-11931S
Institucionální podpora: RVO:67985823
Klíčová slova: neonatal rat * clonazepam * GABA(A)/BZD receptor binding * GABA(B)receptor binding * subunit mRNA expression
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 5.924, rok: 2020
Způsob publikování: Open access
https://www.mdpi.com/1422-0067/21/9/3184

Benzodiazepines (BZDs) are widely used in patients of all ages. Unlike adults, neonatal animals treated with BZDs exhibit a variety of behavioral deficits later in life, however, the mechanisms underlying these deficits are poorly understood. This study aims to examine whether administration of clonazepam (CZP, 1 mg/kg/day) in 7-11-day-old rats affects Gama aminobutyric acid (GABA)ergic receptors in both the short and long terms. Using RT-PCR and quantitative autoradiography, we examined the expression of the selected GABA(A) receptor subunits (alpha 1, alpha 2, alpha 4, gamma 2, and delta) and the GABA(B) B2 subunit, and GABA(A), benzodiazepine, and GABA(B) receptor binding 48 h, 1 week, and 2 months after treatment discontinuation. Within one week after CZP cessation, the expression of the alpha 2 subunit was upregulated, whereas that of the delta subunit was downregulated in both the hippocampus and cortex. In the hippocampus, the alpha 4 subunit was downregulated after the 2-month interval. Changes in receptor binding were highly dependent on the receptor type, the interval after treatment cessation, and the brain structure. GABA(A) receptor binding was increased in almost all of the brain structures after the 48-h interval. BZD-binding was decreased in many brain structures involved in the neuronal networks associated with emotional behavior, anxiety, and cognitive functions after the 2-month interval. Binding of the GABA(B) receptors changed depending on the interval and brain structure. Overall, the described changes may affect both synaptic development and functioning and may potentially cause behavioral impairment.
Trvalý link: http://hdl.handle.net/11104/0309870